Year: 2014
Type: article
Abstract: Erythropoietin (EPO) is a hormone that induces red blood cell production. In its recombinant form, EPO is the one of most prescribed drugs to treat anemia, including that arising in cancer patients. In randomized trials, EPO administration to cancer patients has been associated with decreased survival. Here, we investigated the impact of EPO modulation on tumorigenesis. Using genetically engineered mouse models of breast cancer, we found that EPO promoted tumorigenesis by activating JAK/STAT signaling in breast tumor-initiating cells (TICs) and promoted TIC self renewal. We determined that EPO was induced by hypoxia in breast cancer cell lines, but not in human mammary epithelial cells. Additionally, we demonstrated that high levels of endogenous EPO gene expression correlated with shortened relapse-free survival and that pharmacologic JAK2 inhibition was synergistic with chemotherapy for tumor growth inhibition in vivo. These data define an active role for endogenous EPO in breast cancer progression and breast TIC self-renewal and reveal a potential application of EPO pathway inhibition in breast cancer therapy.
DOI: 10.1172/jci69804
Language: English
Subfield: Hematology
Field: Medicine
Domain: Health Sciences
Open Access status: bronze
Funders: California Institute for Regenerative Medicine, Damon Runyon Cancer Research Foundation, National Institutes of Health, University of North Carolina at Chapel Hill, National Heart, Lung, and Blood Institute, National Institute of Mental Health, National Cancer Institute, National Institute of General Medical Sciences, National Institute of Environmental Health Sciences, Center for Gastrointestinal Biology and Disease, School of Medicine, University of North Carolina at Chapel Hill
Awards: G1017297203, G1111229574, G1192852400, G1650492066, G1666267328, G1757064810, G3351074004, G3724751891, Stanford CIRM Training Program, G5520316217, G5850682332, G6374234983, G9000037730, G9000157954, G9000343034, Cancer Center Support Grant, Pre-doctoral Training Program in Integrative Vascular Biology, Cancer Center Support Grant
OpenAlex ID: W2069264184